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(Circulation. 1997;95:1015-1021.)
© 1997 American Heart Association, Inc.

Articles

Effects of GP IIb/IIIa Receptor Monoclonal Antibody (7E3), Heparin, and Aspirin in an Ex Vivo Canine Arteriovenous Shunt Model of Stent Thrombosis

Raj R. Makkar, MD; Frank Litvack, MD; Neal L. Eigler, MD; Masato Nakamura, MD; Pamela A. Ivey, MD; James S. Forrester, MD; Prediman K. Shah, MD; Robert E. Jordan, PhD; Sanjay Kaul, MD

the Cardiovascular Interventional Research Center, the Division of Cardiology, Department of Medicine, The Burns and Allen Research Institute, Cedars-Sinai Medical Center, and UCLA School of Medicine, Los Angeles, Calif, and Centocor Inc, Malvern, Pa (R.E.J.).

Correspondence to Sanjay Kaul, MD, Division of Cardiology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048. E-mail kaul@csmc.edu.

Background Thrombosis is an important limitation of metallic coronary stents, especially in smaller vessels in which shear rates are high. Monoclonal antibody to platelet glycoprotein IIb/IIIa receptor (7E3) has been shown to inhibit shear-induced platelet aggregation. In this study, we compared the effects of 7E3, heparin, and aspirin on stent thrombosis in an ex vivo arteriovenous shunt model of high-shear blood flow.

Methods and Results An ex vivo arteriovenous shunt was created in 10 anesthetized dogs. Control rough-surface slotted-tube nitinol stents (n=72) expanded to 2 mm in diameter in a tubular perfusion chamber were interposed in the shunt and exposed to flowing arterial blood at a shear rate of 2100 s^-1 for 20 minutes. The animals were treated with intravenous murine 7E3 (Fab')₂ (0.2, 0.4, and 0.8 mg/kg), heparin (100 U/kg), or aspirin (10 mg/kg). Effects of the test agents on thrombus weight, platelet aggregation, platelet P-selectin expression, bleeding time, and activated clotting time (ACT) were quantified. 7E3 reduced stent thrombosis by 95% (20±1 to 1±1 mg, P<.001) and platelet aggregation by 94% (14±2 to 1±1 , P<.001) at the highest dose (0.8 mg/kg). 7E3 significantly prolonged bleeding time but had no effect on ACT and platelet P-selectin expression. Heparin prolonged ACT but had no significant effect on stent thrombosis or platelet aggregation. Aspirin, although it inhibited platelet aggregation by 65%, had no effect on stent thrombosis (19±2 versus 20±1 mg in controls).

Conclusions 7E3 produced a dose-dependent inhibition of acute stent thrombosis under high-shear flow conditions. Stent thrombosis was resistant to heparin and aspirin. Thus, 7E3 may be an effective agent for preventing stent thrombosis.

Key Words: platelets • angioplasty • thrombosis

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